Scn1b deletion leads to increased tetrodotoxin-sensitive sodium current, altered intracellular calcium homeostasis and arrhythmias in murine hearts

The Journal of Physiology
Xianming LinMario Delmar

Abstract

Na(+) current (INa) results from the integrated function of a molecular aggregate (the voltage-gated Na(+) channel complex) that includes the β subunit family. Mutations or rare variants in Scn1b (encoding the β1 and β1B subunits) have been associated with various inherited arrhythmogenic syndromes, including Brugada syndrome and sudden unexpected death in patients with epilepsy. We used Scn1b null mice to understand better the relation between Scn1b expression, and cardiac electrical function. Loss of Scn1b caused, among other effects, increased amplitude of tetrodotoxin-sensitive INa, delayed after-depolarizations, triggered beats, delayed Ca(2+) transients, frequent spontaneous calcium release events and increased susceptibility to polymorphic ventricular arrhythmias. Most alterations in Ca(2+) homeostasis were prevented by 100 nM tetrodotoxin. We propose that life-threatening arrhythmias in patients with mutations in Scn1b, a gene classically defined as ancillary to the Na(+) channel α subunit, can be partly consequent to disrupted intracellular Ca(2+) homeostasis. Na(+) current (INa) is determined not only by the properties of the pore-forming voltage-gated Na(+) channel (VGSC) α subunit, but also by the integrated functio...Continue Reading

References

Apr 20, 1990·Science·W J LedererR W Hadley
Jun 3, 2000·Nature Genetics·C I RodríguezS M Dymecki
Aug 19, 2000·Circulation Research·G E Morley, J Jalife
May 9, 2002·The Journal of Biological Chemistry·Jyoti D MalhotraLori L Isom
Nov 5, 2003·Journal of Molecular and Cellular Cardiology·Marion J ThomasOle Petter Ottersen
Jan 22, 2004·Journal of Clinical Neurophysiology : Official Publication of the American Electroencephalographic Society·Renzo Guerrini, Jean Aicardi
Apr 23, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Chunling ChenLori L Isom
Jun 5, 2004·Proceedings of the National Academy of Sciences of the United States of America·Peter J MohlerVann Bennett
Jul 26, 2005·Biochemical and Biophysical Research Communications·Hervé Duclohier
Jan 24, 2006·American Journal of Physiology. Heart and Circulatory Physiology·Sergey F MironovArkady M Pertsov
Aug 15, 2006·Biochemical and Biophysical Research Communications·Fabien Brette, Clive H Orchard
Nov 23, 2006·Nature Reviews. Neuroscience·Stephen G Waxman
Apr 26, 2007·Cleveland Clinic Journal of Medicine·Stephan U SchueleHans O Lüders
Jun 20, 2007·Nature Cell Biology·Doo Yeon KimDora M Kovacs
Dec 6, 2007·Circulation Journal : Official Journal of the Japanese Circulation Society·Sami F NoujaimJosé Jalife
Aug 1, 2007·Neurology·S U SchueleN Foldvary-Schaefer
Sep 18, 2007·Genesis : the Journal of Genetics and Development·Chunling ChenLori L Isom
Sep 22, 2007·Journal of Molecular and Cellular Cardiology·Luis F Lopez-SantiagoLori L Isom
Jul 30, 2008·Pharmacology & Therapeutics·Antonio ZazaJohn C Shryock
Aug 12, 2009·Nature Reviews. Neurology·Rainer SurgesJosemir W Sander
Aug 28, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Gustavo A PatinoLori L Isom
Apr 7, 2010·Science Translational Medicine·A M GoldmanJ L Noebels
Jun 8, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Alexey V GlukhovIgor R Efimov
Oct 26, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Cynthia GershomeGlen F Tibbits
Apr 8, 2011·Epilepsia·Charlotte Dravet
Apr 8, 2011·Epilepsia·Pierre GentonCharlotte Dravet
Apr 8, 2011·Epilepsia·John C OakleyWilliam A Catterall
Jul 9, 2011·Lancet·Simon Shorvon, Torbjorn Tomson
Jul 20, 2011·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Xianming LinMario Delmar
Sep 29, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sami F NoujaimJosé Jalife

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Citations

Mar 17, 2015·The Journal of Physiology·Donald M Bers, Ye Chen-Izu
Oct 24, 2015·Epilepsia·Samden LhatooUNKNOWN NINDS Center for SUDEP Research
Jul 5, 2017·Forensic Sciences Research·Yeda WuJianding Cheng
Mar 4, 2020·International Journal of Molecular Sciences·Michelle M MonaskyCarlo Pappone
Jul 8, 2020·Biomolecules·Samantha C SalvageAntony P Jackson
Oct 30, 2016·Proceedings of the National Academy of Sciences of the United States of America·Chad R FrasierLori L Isom
Dec 16, 2016·Physiological Reviews·Christopher L-H Huang
Aug 5, 2017·Annual Review of Neuroscience·MacKenzie A Howard, Scott C Baraban
May 10, 2018·Frontiers in Physiology·Nnamdi Edokobi, Lori L Isom
Feb 15, 2017·The Journal of Physiology·Rengasayee VeeraraghavanPrzemysław B Radwański
Sep 21, 2018·Frontiers in Physiology·Przemysław B RadwańskiRengasayee Veeraraghavan
Aug 22, 2018·Annals of Clinical and Translational Neurology·Chunling ChenLori L Isom
Nov 3, 2016·American Journal of Physiology. Heart and Circulatory Physiology·Qin XuRichard D Veenstra
Jun 3, 2016·Cold Spring Harbor Perspectives in Biology·Larisa C Kruger, Lori L Isom
Feb 19, 2017·Circulation. Arrhythmia and Electrophysiology·Amara Greer-ShortSeth H Weinberg
Apr 15, 2017·Circulation. Arrhythmia and Electrophysiology·Zhenjiang YangKatherine T Murray
Dec 10, 2020·Chemical Reviews·Cheng ZhuLane A Baker
Oct 9, 2021·American Journal of Physiology. Heart and Circulatory Physiology·Xiaobo WuSteven Poelzing
May 27, 2021·Human Heredity·Hisham Al-WardHui Xu

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